In this work we showed that CPT and TPT inhibit human endothelial cell growth in vitro in a non-cytotoxic manner and that this inhibition lasts more than 96 h after drug removal. We also showed that LCPT and TPT, unlike a nonspecific cytotoxic agent, cisplatin, are as effective as TNP-470 in inhibiting angiogenic growth in the in vivo disc angiogenesis model. From this observation we propose that in addition to their proven tumoricidal activities, camptothecins may have an indirect in vivo antitumor effect mediated through the inhibition of angiogenesis.

2 AbstractPurpose: Fast-track surgery or Enhanced Recovery Programmes (ERP) have been shown to improve patient outcomes with shorter post-operative recovery times, fewer complications and more cost-effective care amongst the reported benefits. Traditionally the effectiveness of ERPs have been assessed by measuring clinical outcomes, with the patient experience often being neglected. The aim of this qualitative study was to ascertain patients' expectations and experiences of fast track surgery and recovery at home within the setting of an Enhanced Recovery Programme (ERP).Method: 20 patients enrolled in the treatment group of the randomised controlled trial 'Enhanced recovery in liver resection surgery' were interviewed pre-operatively and 6 weeks post-surgery. Transcripts were analysed using Thematic Analysis.Results: Patients approached the surgery with a sense of renewed hope. Involvement with the ERP was viewed positively and having milestones to aim for gave patients a sense of purpose. Many felt that real recovery from surgery began at home and so felt positive about having an early discharge. Patients did report some concerns about being discharged early and those who failed to meet milestones or were readmitted to hospital experienced this as failure.Conclusions: This qualitative data demonstrates some of the complexities of patients' expectations and experiences of the ERP. Whilst patients generally experience the ERP positively, they also have concerns about the process. The study highlights areas where additional support may be needed for patients enrolled in ERPs and discharged early.Keywords: qualitative research, enhanced recovery programmes, liver cancer, discharge from hospital The final publication is available at Springer via http://dx

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Activation of endothelial cell integrins inhibits DNA breakage by diverse agents, including the DNA-damaging agent bleomycin. DNA breaks activate nuclear poly(ADP-ribose) polymerase (PARP), which regulates chromatin structure and DNA repair. We determined the role of PARP in suppression of bleomycin genotoxicity by integrins using wild-type and PARP knockout mouse lung endothelial cells (MLEC), and the PARP inhibitor, 3-aminobenzamide (3AB). Activation of beta1 integrins by antibody clustering enhanced the sensitivity of wild-type nuclei to digestion with micrococcal nuclease and deoxyribonuclease I, indicating that chromatin structure was altered. 3AB blocked this effect. Knockout and 3AB-treated wild-type MLEC were hypersensitive to deoxyribonuclease I compared with wild-type cells, demonstrating that PARP regulates chromatin structure. Integrin clustering reduced the hypersensitivity of knockout cells, suggesting additional, PARP-independent mechanisms that inhibit nuclease interaction with chromatin. Bleomycin caused DNA breakage in wild-type and knockout MLEC. Breaks were eliminated after 60 min incubation of wild-type cells in drug-free medium, whereas 3AB or PARP knockout inhibited DNA repair. Integrin clustering protected wild-type cells from DNA breakage, and 3AB and PARP knockout inhibited this protection. Bleomycin caused large increases in PARP activity in wild-type but not knockout MLEC, and integrin clustering inhibited the activation of PARP. The results indicate that the antigenotoxic effects of integrin activation require PARP and that integrins alter chromatin structure by PARP-dependent and -independent mechanisms.